Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase

Arsun Bektas, Yongqing Zhang, Elin Lehmann, William H. Wood, Kevin G. Becker, Karen Madara, Luigi Ferrucci, Ranjan Sen

Research output: Contribution to journalArticle

Abstract

Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dys-regulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation gene expression mediated by the transcription factor NF-κB is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-κB -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-κB up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3- kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dys-regulated basal NF-κB activity may contribute to the mild pro-inflammatory state of aging.

Original languageEnglish (US)
Pages (from-to)957-974
Number of pages18
JournalAging
Volume6
Issue number11
StatePublished - 2014
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinases
Phosphatidylinositol 3-Kinase
Cytokines
T-Lymphocytes
Sirolimus
Interleukin-1
Chemokines
Transcription Factors
Up-Regulation
Gene Expression

Keywords

  • CD4+ T cells
  • Gene expression
  • Human aging
  • NF-κB
  • PI3K

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Bektas, A., Zhang, Y., Lehmann, E., Wood, W. H., Becker, K. G., Madara, K., ... Sen, R. (2014). Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. Aging, 6(11), 957-974.

Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. / Bektas, Arsun; Zhang, Yongqing; Lehmann, Elin; Wood, William H.; Becker, Kevin G.; Madara, Karen; Ferrucci, Luigi; Sen, Ranjan.

In: Aging, Vol. 6, No. 11, 2014, p. 957-974.

Research output: Contribution to journalArticle

Bektas, A, Zhang, Y, Lehmann, E, Wood, WH, Becker, KG, Madara, K, Ferrucci, L & Sen, R 2014, 'Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase', Aging, vol. 6, no. 11, pp. 957-974.
Bektas A, Zhang Y, Lehmann E, Wood WH, Becker KG, Madara K et al. Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. Aging. 2014;6(11):957-974.
Bektas, Arsun ; Zhang, Yongqing ; Lehmann, Elin ; Wood, William H. ; Becker, Kevin G. ; Madara, Karen ; Ferrucci, Luigi ; Sen, Ranjan. / Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. In: Aging. 2014 ; Vol. 6, No. 11. pp. 957-974.
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